Vacuum-engineered living probiotics deliver superoxide dismutase to reprogram redox and microbiota networks for gut–immune–brain restoration in chronic inflammatory bowel disease

• Vacuum processing loads antioxidant enzyme inside a mucus-adapted probiotic carrier. • Construct survives gastric transit and releases active enzyme in the intestine. • Therapy reduces oxidative stress and mucosal inflammation in zebrafish colitis. • Microbiota remodeling parallels recovery of anxiety behavior in colitis zebrafish. Inflammatory bowel disease (IBD) arises from oxidative stress, immune dysregulation, and microbial imbalance, and often extends to neuropsychiatric comorbidities via gut–immune–brain axis disruption. Here we present Akkermansia muciniphila engineered by vacuum-assisted intracellular loading of superoxide dismutase (SOD@AKK) as a living therapeutic for chronic IBD. Unlike free SOD, SOD@AKK withstood gastric stress and enabled sustained intestinal release of active enzyme. In a chronic zebrafish IBD model, SOD@AKK markedly reduced oxidative burden, suppressed pro-inflammatory cytokines, restored epithelial integrity, and rebalanced microbial communities. Notably, it also alleviated anxiety-like behavior, linking ecological and immunological repair to behavioral recovery. These findings establish SOD@AKK as a site-specific, multi-functional bio-intervention that integrates redox detoxification with microbiota reprogramming, offering a blueprint for next-generation microbiome-based therapeutics in IBD and related neuroimmune disorders.